Understanding and Controlling Adverse Effects in Myeloma Patients treated with T Cell Redirecting Immunotherapies

Multiple Myeloma, a cancer of the plasma cells in the bone marrow, is the third most common blood cancer in Europe. Despite recent advanced in treatment that has increased survival, it is still an incurable disease, and most patients suffer multiple relapses and will eventually develop resistance to treatment. T cell redirecting therapies such as CART and Bispecific Antibodies (BsAb) have given encouraging results in clinical trials with heavily pretreated patients and several of these have now been approved for clinical use. However, there are side effects associated with these treatments. Many patients treated with bispecific antibodies suffer severe infections, CRS and ICANs are not uncommon, and patients treated with GPRC5D targeted bispecific antibodies lose weight as taste commonly disappears, and in addition develop severe nail and skin disorders. Although adverse effects are recorded in clinical studies, there is limited knowledge about the cellular and molecular events behind these side effects and what can be done to prevent or limit them them.

Many of the patients participating in clinical studies with T cell directed therapies have now been followed for several years and it would be of use to the community to collect and gather information about adverse effects in accessible review papers. New clinical trials are also in progress where T cell redirecting therapies are combined with other drugs. In addition, data on adverse effects in clinical trials on different patient groups treated with bispecific antibodies are now emerging. Bispecific antibodies and well as CAR T are now in use in the clinic in many countries and real world evidence data are emerging. It would be very useful for the community to have access to such data.

Finally, in the past couple of years, papers have been published on how immune responses to bispecific antibodies and CAR-T cells differ between in non-responders, patients with early relapse and those with a prolonged response. Although there is knowledge emerging on how BCMA targeted therapies can lead to susceptibility to infections, there is certainly a need to understand the mechanisms behind adverse effects better. This could lead to now treatment strategies that would benefit patients.

The scope of this Research Topic encompasses, but is not limited to, the following subthemes:

-Adverse effects in clinical studies with patients treated with bispecific antibodies and CAR-T. Of particular interest is susceptibility to infection, what type of treatment can lead to increased rates of infections and what patients are most susceptible. This could be done in a review article.
- A description of types of types of pathogen (bacterial, viral, fungal) patients suffer from and how this is associated with treatment. Information such as the strain of pathogen would be useful. Here an original report from data from real world evidence would be nice. There is also limited data on response to vaccination in these patients and how they respond to treatment to limit infection such as intravenous gammaglobulin injections.
-GPRC5D targeted bispecific antibody – what is the mechanism behind adverse effects and can something be done to prevent them

Please note that Dr. Jakub Krejcik received financial support from BMS and that Dr. Tuna Mutis has received project funds from Genmab, Jannsen Pharmacotherapeutics, and Takeda in the last 5 years. Also note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic.